ALA‐PDT regulates macrophage M1 polarization via ERK/MAPK‐NLRP3 pathway to promote the early inflammatory response

MAPK/ERK通路 巨噬细胞极化 促炎细胞因子 M2巨噬细胞 细胞生物学 吞噬作用 巨噬细胞 癌症研究 信号转导 化学 生物 免疫学 炎症 生物化学 体外
作者
Liqun Wang,Wentao Zhang,Ruiyan Cen,Chenda Yue,Tianzhen Xiao,Yumeng Deng,Lingfei Li,Kedai Sun,Xia Lei
出处
期刊:Lasers in Surgery and Medicine [Wiley]
卷期号:54 (10): 1309-1320 被引量:6
标识
DOI:10.1002/lsm.23618
摘要

Abstract Background Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. Methods In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg‐1), CD206, iNOS, CD86, and inflammatory factors IL‐6, TNF‐α, and IL‐1β by reverse transcription‐polymerase chain reaction and Western blot, Milliplex microtubule‐associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal‐regulated kinase/mitogen‐activated protein kinase (ERK/MAPK) and NOD‐like receptor protein 3 (NLRP3) inflammasome. Results 5‐Aminolevulinic acid (ALA)‐PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg‐1/CD206 in RAW264.7 cells, while, proinflammatory factors IL‐6, TNF‐α, and IL‐1β expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK‐NLRP3 pathway. Conclusion ALA‐PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK‐NLRP3 pathway. It also promotes macrophage phagocytosis.
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